This proposal requests support for a Gordon Research Conference on Epigenetic Regulation of Gene Expression to be held at Holderness School, New Hampshire, August 12-17, 2001. Epigenetic regulation is mediated by the creation and maintenance of heritable, but potentially reversible, changes in chromatin structure and/or DNA methylation which alters gene expression without altering DNA sequence. Epigenetic effects have been discovered in many organisms and they comprise some of the most intriguing and actively investigated phenomena with relevance to both basic and applied science. For example, epigenetic silencing of transgenes poses problems for the long term, commercial use of transgenic plants engineered to express novel phenotypes and can complicate human gene therapy trials. Moreover, loss of epigenetically imprinted events on the chromosome are shown to cause many human cancer types. In addition, mutations in genes encoding DNA methyltransferase and a methyl-DNA binding protein lead to diseases in humans, namely ICF syndrome and Rett Syndrome, respectively. Advances have been made towards understanding the molecular mechanisms that underlie epigenetic silencing in the last few years and this will be a major focus of this conference. Invited speakers are leading researchers working on fungal, plant and animal models who will cover topics such as control and function of DNA methylation, chromatin-based gene silencing, post-transcriptional gene silencing, imprinting, X-inactivation, prions, epigenetics and disease, genome defense systems, paramutation and position effects. The Epigenetics Gordon Conference provides a unique opportunity for researchers working on related phenomena in different organisms to come together and exchange recent results and ideas. It is in a cross-disciplinary environment such as this that intellectual leaps occur and innovative ideas flourish.